Sodium Carbonate → 6-chloro-7-(3-fluorophenyl)-N2-(1,1,1-trifluoro-2-methylpropan-2-yl)-3,4-dihydropyrrolo[1,2-a]pyrazine-2,8(1H)-dicarboxamide

HRID 589837Notes

Reaction equation

HRID 589837 reaction equation
[Cl:1][C:2]1[N:6]2[CH2:7][CH2:8][NH:9][CH2:10][C:5]2=[C:4]([C:11]([NH2:13])=[O:12])[C:3]=1[C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([F:20])[CH:15]=1.[F:21][C:22]([F:40])([F:39])[C:23]([NH:26][C:27](=O)[O:28]C1C=CC([N+]([O-])=O)=CC=1)([CH3:25])[CH3:24].C(=O)([O-])[O-].[Na+].[Na+].[OH-].[Na+]>C(#N)C>[Cl:1][C:2]1[N:6]2[CH2:7][CH2:8][N:9]([C:27]([NH:26][C:23]([CH3:25])([CH3:24])[C:22]([F:40])([F:39])[F:21])=[O:28])[CH2:10][C:5]2=[C:4]([C:11]([NH2:13])=[O:12])[C:3]=1[C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([F:20])[CH:15]=1

Participants

6

Reactant 4

HCID 10340Sodium CarbonateHCID 14798Sodium HydroxideHCID 665839426-Chloro-7-(3-fluorophenyl)-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine-8-carboxamideHCID 665841014-Nitrophenyl 1,1,1-trifluoro-2-methylpropan-2-ylcarbamate

Product 1

HCID 665848396-chloro-7-(3-fluorophenyl)-N2-(1,1,1-trifluoro-2-methylpropan-2-yl)-3,4-dihydropyrrolo[1,2-a]pyrazine-2,8(1H)-dicarboxamide

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
65 °C

Procedure

A suspension of 0.165 (0.56 mmol) of 6-chloro-7-(3-fluorophenyl)-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine-8-carboxamide, 0.197 g (0.67 mmol) of 4-nitrophenyl 1,1,1-trifluoro-2-methylpropan-2-ylcarbamate and 0.155 (1.12 mmol) of sodium carbonate in 3 ml of acetonitrile is heated at 65° C. for 1 hour 30 minutes. After cooling, the mixture is poured into aqueous 1N sodium hydroxide solution and the product is extracted with dichloromethane. After drying over sodium sulfate and filtering, the solvent is evaporated off under reduced pressure and the residue is purified by chromatography on a column of 24 g of silica gel, eluting with a mixture of 3% methanol in dichloromethane, to give 0.125 g of 6-chloro-7-(3-fluorophenyl)-N2-(1,1,1-trifluoro-2-methylpropan-2-yl)-3,4-dihydropyrrolo[1,2-a]pyrazine-2,8(1H)-dicarboxamide in the form of a white powder after crystallization from 4 ml of acetonitrile, filtering off and drying under reduced pressure.

Workup

  1. temperatureAfter cooling
  2. extractionthe product is extracted with dichloromethane
  3. dry with materialAfter drying over sodium sulfate
  4. filtrationfiltering
  5. customthe solvent is evaporated off under reduced pressure
  6. customthe residue is purified by chromatography on a column of 24 g of silica gel
  7. washeluting with a mixture of 3% methanol in dichloromethane

Sources & evidence

ORD record
ord-f11543c59393426ba369e16509beeedb
Source dataset
uspto-grants-2016_01
Patent number
US09233965B2

Reaction notes

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